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The mission was founded on September 8, 1771 by fathers Pedro Cambon and Angel Somera. The planned site for the Mission was along the banks of the Río de los Temblores (the River of the Earthquakes—the Santa Ana River). The priests chose an alternate site on a fertile plain located directly alongside the Rio Hondo in the Whittier Narrows. The site of the Misión Vieja (or "Old Mission") is located near the intersection of San Gabriel Boulevard and Lincoln Avenue in Montebello, California (known to the natives as Shevaanga).
In 1776, a flash flood destroyed much of the crops and ruined the Mission complex, which was subsequently relocated five miles closer to the mountains in present-day San Gabriel (the native settlement of 'Iisanchanga). The Mission is the base from which the pueblo that became the City of Los Angeles, California was sent. On December 9, 1812 (the "Feast Day of the Immaculate Conception of the Blessed Virgin"), a series of massive earthquakes shook Southern California.
The 1812 Wrightwood earthquake caused the three-bell campanario, located adjacent to the chapel's east façade, to collapse. A larger, six-bell structure was subsequently constructed at the far end of the capilla. While no pictorial record exists to document what the original structure looked like, architectural historian Rexford Newcomb deduced the design and published a depiction in his 1916 work The Franciscan Mission Architecture of Alta California.